ArticlePloS one2014
NOD2/RICK-dependent β-defensin 2 regulation is protective for nontypeable Haemophilus influenzae-induced middle ear infection.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Systems perspectives on pediatric otitis media: environmental exposures, genetic susceptibility, and biomarker-guided interventions.Frontiers in pediatrics · 2026Review
- Pattern recognition receptor signaling in otitis media: immune crosstalk and pathogenic mechanisms.Frontiers in immunology · 2026Review
- Mechanisms and regulation of defensins in host defense.Signal transduction and targeted therapy · 2023Review
- The Roles of NOD-like Receptors in Innate Immunity in Otitis Media.International journal of molecular sciences · 2022Review
- Immunomodulation as a Protective Strategy in Chronic Otitis Media.Frontiers in cellular and infection microbiology · 2022Article
- Article
- Innate Immunity in the Middle Ear Mucosa.Frontiers in cellular and infection microbiology · 2021Review
- Article
- Panel 3: Genomics, precision medicine and targeted therapies.International journal of pediatric otorhinolaryngology · 2020Review
- COPD-Related Modification to the Airway Epithelium Permits Intracellular Residence of NontypeableInternational journal of chronic obstructive pulmonary disease · 2020Article
- NOD1/NOD2-mediated recognition of non-typeableInnate immunity · 2019Article
- Deoxynivalenol Impairs Porcine Intestinal Host Defense Peptide Expression in Weaned Piglets and IPEC-J2 Cells.Toxins · 2018Article
- Panel 4: Report of the Microbiology Panel.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2017Review
- Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW1 as an Intracellular Invasion Locus in Haemophilus influenza.PLoS pathogens · 2016Article
- Innate Immunity: Orchestrating Inflammation and Resolution of Otitis Media.Current allergy and asthma reports · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Middle ear infection, otitis media (OM), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. Previously, we have demonstrated that the human middle ear epithelial cells up-regulate β-defensin 2, a model innate immune molecule, in response to nontypeable Haemophilus influenzae (NTHi), the most common OM pathogen, via TLR2 signaling. NTHi does internalize into the epithelial cells, but its intracellular trafficking and host responses to the internalized NTHi are poorly understood. Here we aimed to determine a role of cytoplasmic pathogen recognition receptors in NTHi-induced β-defensin 2 regulation and NTHi clearance from the middle ear. Notably, we observed that the internalized NTHi is able to exist freely in the cytoplasm of the human epithelial cells after rupturing the surrounding membrane. The human middle ear epithelial cells inhibited NTHi-induced β-defensin 2 production by NOD2 silencing but augmented it by NOD2 over-expression. NTHi-induced β-defensin 2 up-regulation was attenuated by cytochalasin D, an inhibitor of actin polymerization and was enhanced by α-hemolysin, a pore-forming toxin. NOD2 silencing was found to block α-hemolysin-mediated enhancement of NTHi-induced β-defensin 2 up-regulation. NOD2 deficiency appeared to reduce inflammatory reactions in response to intratympanic inoculation of NTHi and inhibit NTHi clearance from the middle ear. Taken together, our findings suggest that a cytoplasmic release of internalized NTHi is involved in the pathogenesis of NTHi infections, and NOD2-mediated β-defensin 2 regulation contributes to the protection against NTHi-induced otitis media.
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